Major histocompatibility complex (MHC) molecules are cell surface receptors that present antigen to immune cells in vertebrates. MHC molecules are classified as class I and class II. In general, MHC class II-bearing cells present antigen to CD4+ helper T cells. Humans possess three distinct MHC class II isotypes: DR, for which approximately 70 different allotypes are known; DQ, for which 33 different allotypes are known; and DP, for which 47 different allotypes are known. Each individual bears two to four DR alleles, two DQ alleles, and two DP alleles.
MHC molecules (both class I and class II) participate in the obligate first step of immune recognition by binding small protein fragments (peptides) derived from pathogens or other non-host sources, and presenting these peptides to the regulatory cells (T cells) of the immune system. In the absence of MHC presentation, T cells are incapable of recognizing pathogenic material. Cells that express MHC class II receptors are termed antigen presenting cells (APC). APCs ingest pathogenic organisms and other foreign materials by enveloping them in endosomic vesicles, then subjecting them to enzymatic and chemical degradation. Foreign proteins which are ingested by APCs are partially degraded or "processed" to yield a mixture of peptides, some of which are bound by MHC class II molecules that are en route to the surface. Once on the cell surface, MHC-bound peptides are available for T cell recognition.
Infection with HIV-1 is characterized by a quantitative decline in CD4+ lymphocyte number as well as a qualitative impairment in CD4+ lymphocyte function (Murray et al., N Engl J Med 310:883-889 [1984]; Epstein et al., J Infect Dis 152:727-733 [1985]; and Lane et al., N Engl J Med 313:79-84 [1985]). Immunological abnormalities in helper T cell function occur early, during the asymptomatic phase of infection and prior to the loss in CD4+ cell number (Miedema et al., J Clin Invest 82:1908-1914 [1988]; Laurence et al., J Clin Invest 83:1843-1848 [1989]; and Clerici et al., Nature 339:383 [1989]). Loss of T cell function in vitro predicts both progression to AIDS and survival time (Roos et al., J Infect Dis 171:531-536 [1994]; and Dolan et al., J Infect Dis 172:79-87 [1995]). In addition to these general defects in lymphocyte function, infection typically fails to induce detectable HIV-1-specific proliferative responses (Miedema et al., Immunol Rev 140:35-72 [1994]). When such responses have been observed, they are typically weak, with stimulation indices rarely greater than five (Wharen et al., J Virol 61:2017-2023 [1987]; Berzofsky et al., Nature 334:706-708 [1988]; Krowka et al., J Clin Invest 83:1198-1203 [1989]; Schrier et al., J Immunol 142:1166-1176 [1989]; Schwartz et al., AIDS Res Hum Retro 10:1703-1711 [1994]; and Pontesilli et al., AIDS Res Hum Retro 10:113-114 [1994]).